This project will use newly developed chemically specific, non-invasive magnetic resonance spectroscopic methods to study cerebral metabolism in humans. 1H methods will be used to study the rate of decline of brain phenylalanine in young adult phenylketonurics who go on a low-phenylalanine diet after having chosen previously not to follow such a diet, and to search for evidence of lipid degradation in patients with stroke and dementia. Combined 1H and 13C methods will be used to monitor rates of entry of 13C and eventual steady state 13C fractional enrichment in amino acid and elevated lactate pools when 13C-labeled glucose is given intravenously. The range of variation of amino acid labeling and optimum 1-13C-glucose infusion schedules will be determined in normal subjects of varying age and weight during quiet wakefulness, and then during sensory stimulation and in patients with dementia and complex partial epilepsy. Cerebral lactate elevated by stroke will be studied to evaluate it steady state 13C fractional enrichment as a measure of an ischemic penumbra. The results are expected to provide new information about normal cerebral metabolism and about how the pathophysiological processes at work in dementia, stroke, and epilepsy affect the rate of glucose entry into the brain, the metabolic activity of elevated lactate pools, and rates of amino acid turnover.